title: Peroxisome protein transportation affects metabolism of branched-chain fatty acids that critically impact growth and development of C. elegans.
abstract: The impact of specific lipid molecules, including fatty acid variants, on cellular and developmental regulation is an important research subject that remains under studied. Monomethyl branched-chain fatty acids (mmBCFAs) are commonly present in multiple organisms including mammals, however our understanding of mmBCFA functions is very limited. C. elegans has been the premier model system to study the functions of mmBCFAs and their derived lipids, as mmBCFAs have been shown to play essential roles in post-embryonic development in this organism. To understand more about the metabolism of mmBCFAs in C. elegans, we performed a genetic screen for suppressors of the L1 developmental arrest phenotype caused by mmBCFA depletion. Extensive characterization of one suppressor mutation identified prx-5, which encodes an ortholog of the human receptor for the type-1 peroxisomal targeting signal protein. Our study showed that inactivating prx-5 function compromised the peroxisome protein import, resulting in an increased level of branched-chain fatty acid C17ISO in animals lacking normal mmBCFA synthesis, thereby restoring wild-type growth and development. This work reveals a novel connection between peroxisomal functions and mmBCFA metabolism.
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado, United States of America.
authors.forename: Rencheng
authors.initials: R
authors.lastname: Wang
authors.forename: Marina
authors.initials: M
authors.lastname: Kniazeva
authors.forename: Min
authors.initials: M
authors.lastname: Han
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002849:Chromatography, Gas; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism*; D005820:Genetic Testing; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D020675:Peroxisomes / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D013489:Suppression, Genetic / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D005227:Fatty Acids; D008565:Membrane Proteins; C000589581:Prx-5 protein, C elegans; D018160:Receptors, Cytoplasmic and Nuclear; C085380:peroxisomal targeting sequence receptor